The objective of the proposed research is to study the interactions at the molecular level between known antineoplastic drugs and cellular macromolecules. Probably the most significant difference between the normal and the malignant cell is that the cancer cell is no longer under the control of the host. We feel there may be more subtle differences between normal and cancer cells and that advantage might be taken of these differences to yield more effective methods for use in cancer chemotherapy. We plan to use simple model cell systems including a bacterial system, a human cell line derived from a carcinoma of the nasopharynx, a Chinese hamster cell line and freshly excised tumor cells for use in organotypic or dispersion culture. Our methods will include standard radioisotope techniques, ultracentrifugation analyses, electron microscopy, chromatographic techniques, genetic analyses, and general biochemical methods.